Modern farming and plant production require a constant string of new and novel means of controlling weeds and other pests. Fields are treated with herbicides to rid them of unwanted plants, allowing efficient production of useful crops. Over generations, however, these unwanted plants naturally develop resistance to the standard arsenal of herbicides. New and novel herbicides are constantly required in order to maintain and improve crop yields, such that people are sufficiently fed and clothed.
Herbicides work through modulation of various physiological functions of plant growth. Modulations in the physiological functions that affect plant growth, development, seasonality, dormancy and reproduction. This damage weakens a plant and occasionally results in death. Many types of damage can be compensated for, such that plants survive despite this damage. However, modulation of particularly critical physiological functions will directly affect a plant's survivability. The nature of these modulations is the basis of commercial herbicide development.
Most commercial herbicides modulate one of the critical physiological functions for plant life such as pigment synthesis, plant root/shoot growth, lipid biosynthesis, photosynthesis, respiration, plant auxin, auxin transporter, cell division, cellulose synthesis, amino acid synthesis and so on. Many of these physiological functions can be inhibited by multiple classes of herbicides. For example, imidazolinones, pyrimidinylthiobenzoate, sulfonylamino-carbonyltriazolinones, sulfonlyureas, and triazolopyrimidines are herbicides that inhibit acetolactate synthesis (ALS), a key enzyme in the biosynthesis of branched amino acids such as isoleucine, leucine and valine (LaRossa and Schloss, 1984). Other examples are phenylcarbamates, pyridazinones, triazinones, uracils, amides, ureas, benzothiadiazinones, nitriles, and phenylpyridazines that are herbicides that inhibit photosynthesis by binding to the QB-binding niche on the D1 protein of photosynthesis II complex in chloroplast thylakoid membranes (Vencill et al., 2012).
Glutamine Synthetase
Glutamine synthetase is a key enzyme in facilitating the condensation of glutamate and ammonium to form glutamine and thus plays a significant role in the metabolism of ammonia in both prokaryotic and eukaryotic cells (reviewed in Eisenberg, 2000).
Extracellular glutamate synthetase has been found to play a significant role in the survival of Mycobacterium tuberculosis (see, for example, Harth et al., 2000). Inhibitors of glutamine synthetase such as L-Methionine sulfoximine and JFD01307SC directed towards M. tuberculosis (Lamichhane et al., 2011) and screening methods for their detection have been developed (see, for example, Singh et al., 2005, 2006, US Patent Appln. Pub. No. 20100022584).
Plant glutamine synthetase (GS) has been found to play a critical role in ammonia metabolism in plants as well (see, for example, Castro-Rodríguez, et al., 2011). It has been found to exist in two isoforms, cytosolic and plastidic.
Inhibiting glutamine synthetase (GS) is one mechanism of action for controlling weeds. Currently, there is only one class of commercial herbicides that has been developed for inhibiting GS, using a key enzyme converting glutamate and ammonium into glutamine (Lea 1984). Phosphinic acids (glufosinate and bialaphos) inhibit the activity of GS, resulting in an accumulation of ammonium in plants (Tachibana 1986). The ammonia destroys the cells and directly inhibits photosynthesis I and II reactions (Vencill et al., 2012) by reducing the pH gradient across the membrane which can uncouple photophosphorylation.
Glufosinate or phosphinothricin is a commercial synthesized product; it is a racemic version of DL-glufosinate-ammonium salt. Glufosinate is sold under trade names Basta, Buster and Liberty.
Bialaphos is a naturally occurring tripeptide herbicide that comes from a soil microorganism, Streptomyces hygroscopicus [Selvakumar et al., 1999]. It is also produced by S. viridochromeogenes (Krainsky) [Blodgett et al., 2008]. Bialaphos is a proherbicide, which has to be metabolized into a phytotoxin: phosphinothricin {4-[hydroxyl(methyl)phosphinoyl]-L-homoalanine]. Phosphinothricin is an irreversible inhibitor of GS. Bialaphos was introduced in Japan in 1984 and it was the first herbicide produced by fermentation. It is commercially available.
One of the strengths of GS inhibition is that crops have been genetically engineered for resistance to the compounds when used as herbicides. Glufosinate or its ammonium salt DL-phosphinothricin is an active ingredient in several nonselective systemic herbicides such as BASTA®, RELY®, FINALE®, IGNITE®, CHALLENGE®, AND LIBERTY®. Bayer Company has marketed such crops under the LIBERTY LINK® trademark to be used with their glufosinate herbicide. Glufosinate-treated plants die due to a buildup of ammonia and a cessation of photosynthesis due to lack of glutamine.
Burkholderia 
The bacterial species in the genus Burkholderia are ubiquitous in soil, rhizosphere, insects, fungus and water (Coenye and Vandamme, 2003; Parke and Gurian-Sherman, 2001). The Burkholderia genus, β-subdivision of the proteobacteria, comprises more than 40 species that inhabit diverse ecological niches (Compant et al. 2008). Traditionally, they have been known as plant pathogens, B. cepacia being the first one discovered and identified as the pathogen causing disease in onions (Burkholder, 1950). Several Burkholderia species have developed beneficial interactions with their plant hosts (see, for example, Cabballero-Mellado et al., 2004, Chen et al., 2007). Some Burkholderia species have also been found to be opportunistic human pathogens; see, for example, Cheng and Currie, 2005 and Nierman et al., 2004. Additionally, some Burkholderia species have been found to have potential as biocontrol products (see for example, Burkhead et al., 1994; Knudsen et al., 1987; Jansiewicz et al., 1988; Gouge et al., US20030082147; Parke, U.S. Pat. No. 6,077,505; Cassida, U.S. Pat. No. 6,689,357; Jeddeloh et al., WO2001055398; Zhang et al., U.S. Pat. No. 7,141,407). Some species of in this genus have been effective in bioremediation to decontaminate polluted soil or groundwater (see, for example, Leahy et al. 1996; Lessie et al. 1996). Further, some Burkholderia species have been found to secrete a variety of extracellular enzymes with proteolytic, lipolytic and hemolytic activities, as well as toxins, antibiotics, and siderophores (see, for example, Ludovic et al., 2007; Nagamatsu, 2001; Morita et al., 2003; Okazaki et al., 2004).
Known Secondary Metabolites from Burkholderia 
In a recent review, (Vial et al., 2007) there is discussion of the great diversity and versatility of extracellular compounds produced by the different species of Burkholderia sp. Some of the known toxins produced by Burkholderia sp. include a) toxoflavin (1,6-dimethylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H, 6H)-dione) and fervenulin (a tautomeric isomer of toxoflavin) with antibacterial, antifungal, and herbicidal activities (Jeong, et al., 2003); b) tropolone (2-hydroxy-2,4,6-cycloheptatrien-1-one), a non-benzenoid aromatic compound with both phenolic and acidic moieties and proven antimicrobial, antifungal, and insecticidal properties (Okazaki et al., 2004); c) rhizobitoxin ([2-amino-4-(2-amino-3-hydroxypropoxy)-trans-but-3-enoic-acid]), that, among other phytotoxic effects, induced foliar chlorosis due to inhibition of cystathione-β-lyase (Morita et al., 2003); d) rhizoxin, a macrocyclic polyketide, which kills rice seedlings by binding to β-tubulin, inhibiting the normal cell division cycle (Koga-Ban et al., 1995) and demonstrating broad anti-tumor activity in vitro (Tsuruo et al., 1986); e) bongkrekic acid, which inhibits adenine nucleotide translocase as well as cell apoptosis (Henderso et al., 1970); and f) rhizonin A and B, hepatotoxic cyclopeptides that were first discovered from a fungus (Rhizopus sp.) but later were shown to be produced by a bacterial endosymbiont of the genus Burkholderia (Partida-Martinez et al., 2007).
One of the best characterized antimicrobial and antifungal compounds produced by Burkholderia sp., are cepaciamide (Holmes et al., 1998); cepacidine A (Lee et al., 1994) and related compounds in the xylocandin complex (Meyers et al., 1987); pyrrolnitrin (Burkhead et al 1997; El-Banna et al., 1998) and its derivatives (Sultan et al., 2008) pseudanes (Moon et al., 1996), phenazine (Stead et al., 1996) maculosin and banegasine (Cain et al., 2003); glidobactins such as cepafungin (Shoji et al., 1990); phenylacetic acid, hydrocinnamic acid, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetate methyl ester (Mao et al., 2006). Other antifungal compounds summarized by Vial et al. (2007) include 2-hydroxymethyl-chroman-4-one, oligopeptides called altericidins, capacins A and B, hydrogen cyanide and a wide variety of volatile small molecules. Several Burkholderia strains are also known to produce phytohormones and siderophores such as pyochelin, ornibactin, malleobactin, capabactin, cepaciachelin, effector proteins as well as surface-active glycolipids called rhamnolipids (Abdel-Mawgoud et al., 2010). As in several Gram-negative bacteria, the production of most of the above mentioned secondary metabolites is mediated through N-acylhomoserine lactone (AHSL or AHL) by a process known as quorum sensing (QS; (Keum et al., 2009)). Quorum sensing is a cell-to-cell communication system that perceives and responds to population density in order to coordinate gene expression (Vial et al., 2007). It appears to be present in every Burkholderia strain studied so far (Deng et al., 2010).
Oxazoles, Thiazoles and Indoles
Oxazoles, thiazoles and indoles are widely distributed in plants, algae, sponges, and microorganisms. A large number of natural products contain one or more of the five-membered oxazole, thiazole and indole nucleus/moieties. These natural products exhibit a broad spectrum of biological activity with demonstrable therapeutic value. For example, bleomycin A (Tomohisa et al.), a widely prescribed anticancer drug, effects the oxidative degradation of DNA and uses a bithiazole moiety to bind its target DNA sequences (Vanderwall et al., 1997). Bacitracin (Ming et al., 2002), a thiazoline-containing peptide antibiotic, interdicts bacterial cell wall new biosynthesis by complexation with C55-bactoprenolpyrophosphate. Thiangazole (Kunze et al., 1993) contains a tandem array of one oxazole and three thiazolines and exhibits antiviral activity (Jansen et al., 1992). Other oxazole/thiazole-containing natural products such as thiostrepton (Anderson et al., 1970) and GE2270A (Selva et al., 1997) inhibit translation steps in bacterial protein synthesis. More than 1000 alkaloids with the indole skeleton have been reported from microorganisms. One-third of these compounds are peptides with masses beyond 500 Da where the indole is tryptophan derived. The structural variety of the remaining two-thirds is greater and their biological activity appears to cover a broader range, including antimicrobial, antiviral, cytotoxic, insecticidal, antithrombotic, and enzyme inhibitory activity.